The bacterium Escherichia coli directs the rate of tryptophan biosynthesis either through allosteric control of the enzyme aggregate which catalyzes the earliest specific reactions of the sequence, or through repression of the tryptophan operon at the level of mRNA transcription. A concerted biochemical and genetic study of the enzyme aggregate catalyzing anthranilate formation and utilization has two goals: to elucidate the mode of action of tryptophan as a feedback modifier and to specify the mechanistic details of the aromatization process. Wild-type trp operon DNA contains at least a dozen sequences which can undergo mutation to yield new sites for the initiation of transcription. These promoters, which function even under conditions of repression, lead to levels of expression of distal genes 2-20 fold higher than control values. Genetic analysis of these new promoters is feasible because many of the mutational events result in a total or partial requirement for tryptophan. Experiments will be directed toward obtaining sequence information for these promoter regions through analysis of DNA enriched in new promoter sites and of transcripts prepared from this DNA. Parallel genetic studies will attempt to define any additional cytoplasmic elements functioning in conjunction with each promoter.